The aims of this proposal are to: 1) define the role of phosphorylation of the human immunodeficiency virus (HIV) antigen, p17gag, by cellular and/or viral serine/threonine and tyrosine kinases and 2) to design and test inhibitors of the protein kinases as potential inhibitors of HIV replication or its cytolytic activity. One goal will be to determine whether a viral protein kinases(s) exists, to what gene product it is related and whether it can utilize p56/p17 as a substrate in vitro. A second goal will be to determine whether cellular protein kinases such as protein kinase C and tyrosine protein kinases associated with monocytes and lymphocytes can utilize recombinant p56gag as a substrate in vitro. A third goal of these studies will be to determine whether there is a difference in the phosphoamino acid/phosphopeptide pattern of p56/p17 in vivo betwen H9 cells for which HIV is not cytolytic and ATH-8 cells and peripheral blood lymphocytes which are killed by the virus. The last goal of these studies will be to determine whether any known inhibitors of serine/threonine or tyrosine protein kinases can inhibit HIV replication in H9, ATH-8 or peripheral blood cells in vitro. If this aspect of the study proves fruitful, then computer modeling studies will be carried out to design and synthesize new inhibitors of protein kinases.